Facial transplantation and immunosuppressed patients: a new frontier in reconstructive surgery

Composite tissue transplantation in reconstructing complex facial defects has developed tremendous interest over the recent years, since the first report of partial face transplantation performed in France in 2005. However, the controversy over the ethical, immunological, and psychological issues remains. Recently, we obtained IRB approval to perform partial face transplantation at Brigham & Women's Hospital, Boston. Here we present the rationale and IRB application process of our unique approach to this highly controversial procedure, which focuses on partial face transplantation on patients currently on immunosuppressants due to previous transplanted organ. 'Patient selection criteria', selection process, technical and immunological protocols are discussed. We currently share the concern that life-long immunosuppression associated with facial transplantation may not outweigh its benefits as compared to the alternative reconstructive methods. We asked ourselves the question of which patient population would risk less and overall benefit more from undergoing face transplantation, and identified those currently on immunosuppressive therapy the most suitable candidates. Organ transplant recipients are at increased risk of malignancy, particularly skin cancer commonly located in the facial region, necessitating surgical resection and facial reconstruction. They also have to take immunosuppressants to prevent rejection of their primary transplanted organ, which will minimize the need for additional immunosuppression associated with facial allograft. Being a previous organ recipient also diminishes the difficulty of complying with the strict postoperative immunosuppressive regimen, commonly encountered by organ transplant recipients. This approach could be very beneficial for previously immunosuppressed patients and perhaps take its place in our reconstructive ladder options.     

Psychosocial considerations in facial transplantation

The human face and facial transplantation have long captured the interest and imagination of scientists, the media and the lay public. The face is central to our identity, and our communication with the outside world. It is this great importance we attach to our face that makes facial disfigurement such a devastating condition. Facial transplantation could provide an excellent alternative to current treatments for facial disfigurement caused by burns, trauma, cancer extirpation or congenital birth defects. Herein we discuss some of the principal psychosocial considerations which have preceded the clinical introduction of facial transplantation, and which continue today after cases have been performed world-wide.     

Franti?ek Burian (September 17, 1881–October 15, 1965) and the beginning of plastic surgery in Czechoslovakia

In the Czech Republic, plastic surgery is inseparably related to the name of its initiator and founder, Franti?ek (Francis) Burian, who not only laid the foundations of this branch in Czechoslovakia, but also influenced many contemporary plastic surgeons. Burian spent 6?years as a military surgeon in the Balkan wars and in World War I. Up until World War I, only separate plastic operations by excellent surgeons were mentioned. The experience gained from the First World War led to an undreamed-of development in plastic surgery and to the need for specialisation. It was during the First World War that European plastic surgery was formed as a special branch. Burian probably opened the first department of plastic surgery in the world at the Jedli?ka Institute in 1927. In 1932, after operating for 5?years, the department of plastic surgery at the Jedli?ka Institute was granted the status of a separate clinic.     

Surgeon Scientist

The origins and development of the renal transplant program at the Peter Bent Brigham Hospital (now the Brigham and Women's Hospital) from the late 1940s to the present are reviewed. The program was initiated as a effort to understand hypertension as a cause of renal failure. The initial transplants were unmodified allogeneic grafts placed in the thigh, followed by extensive laboratory experiments on dogs. This research culminated with the first successful human transplant of a kidney between identical twins in 1954. In 1959 the first successful fraternal allogeneic graft was accomplished as part of a protocol utilizing total body irradiation and bone marrow replacement. Finally, with the development of immunosuppressive drugs, we were able to transplant a cadaveric kidney successfully in 1962. This was a major impetus in the study of organ transplantation worldwide, which currently involves kidneys, liver, heart, pancreas, heart/lung, and bone marrow.     

全颜面部深度烧伤的临床治疗

目的探讨提高患者全颜面部深度烧伤创面修复质量的处理方式。方法将54例全颜面部深度烧伤患者分为延期植皮组(48例)和早期切痂组(6例)。伤后3周对延期植皮组患者实施剥、削痂或手术刀柄刮除新生肉芽组织至基底层,在全颜面部分区进行自体中厚皮片移植术;早期切痂组患者于伤后1周行切痂术,其他处理同延期植皮组。观察两组患者首次手术时间、面部手术时间、手术总次数、手术前后血红蛋白(Hb)浓度、术中输血量及出血量,随访观察患者治愈后的情况。结果两组患者的首次手术时间、手术总次数、手术前后Hb浓度及术中输血量比较,差异无统计学意义(P>0．05)。延期植皮组患者面部手术时间为(21．9±3．2)d,较早期切痂组(12．6±1．3)d晚 (P<0．05);延期植皮组术中出血量(98±52)ml/100 cm2,明显少于早期切痂组(331±121)ml/100 cm2(P<0．01)。延期植皮组患者创面愈合后较早期切痂组面部外观丰满,皮肤弹性好,表情丰富。术后两组患者均出现不同程度小口畸形、双眉缺失,80％的患者出现睑外翻,皮片缝接处遗有增生性瘢痕等,经多次整形手术予以矫正。结论全颜面部深度烧伤患者行自体中厚皮片分区移植,创面无论采用早期切痂,还是延期剥、削痂或完全清除新生肉芽组织至基底层,均可取得较为满意的治疗效果;与前者相比,后者术中出血少,术后外观、功能恢复好;同时术后有效的物理治疗和有计划地进行后遗畸形整形手术,也是保障其治疗效果的重要因素。     

Ten years of liver transplantation at Groote Schuur Hospital.

INTRODUCTION: Liver transplantation has evolved from an experimental procedure to being the treatment of choice for many patients with end-stage liver disease, and is performed on a routine basis in most major centres throughout the world. However, certain situations peculiar to developing countries have a major impact on liver transplant programmes in these countries. We present the results of the liver transplant programme in Cape Town. PATIENTS AND METHODS: All patients undergoing orthotopic liver transplantation at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital were included in this report. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the subsequent implantation of the liver. All patients received standardised peri-operative management; in particular, the immunosuppressive protocol consisted of cyclosporin, steroids and azathioprine. Since October 1988, 83 patients have undergone 89 orthotopic liver transplants. There were 44 adults and 39 children, the age range being from 6 months to 56 years. The commonest indications for hepatic transplantation in adults included cryptogenic cirrhosis, auto-immune hepatitis and primary sclerosing cholangitis. In children biliary atresia was the commonest cause of liver failure. RESULTS: Of the 81 patients transplanted, 50 are alive and well with follow-up ranging from 2 months to 9.5 years. The cumulative graft survival rate was 72% at 1 year and 61% at 5 years. Six patients have undergone re-transplantation and 4 patients have had combined liver/kidney transplants. De novo hepatitis due to hepatitis B virus (HBV) has occurred in 8 patients following transplantation. Subsequent investigation has shown that 5 of the donors of these livers were hepatitis B core antibody (HBcAb)-positive, while information on the remaining 3 was not available. Tuberculosis (TB) has been a significant problem in 4 patients, with 2 deaths precipitated by anti-TB drug-induced hepatitis. Post-transplant lymphoproliferative disorder was also responsible for significant postoperative morbidity. CONCLUSION: Orthotopic liver transplantation has been established at Groote Schuur Hospital as the treatment of choice for selected patients with chronic end-stage liver disease. However, hepatitis B and TB appear to present a problem. The particularly high prevalence of HBV carrier status in our donor population may necessitate the use of living donors in the future.     

Herbert Moran Memorial Lecture. World War I: the genesis of craniomaxillofacial surgery?

Herbert Moran enlisted in the Royal Army Medical Corps early in World War I. His autobiography captures the impact of contemporary experience of wartime gunshot wounds, seen in vast numbers and with little understanding of the requirements of wartime surgery. Wounds of the face and brain were numerous, especially in trench fighting. In France, Germany, Britain and elsewhere, surgeons and dentists collaborated to repair mutilated faces and special centres were set up to facilitate this. The innovative New Zealand surgeon Harold Gillies developed his famous reconstructive techniques in the Queen's Hospital at Sidcup, with the help of dental surgeons, anaesthetists and medical artists. The treatment of brain wounds was controversial. Many surgeons, especially on the German side, advocated minimal primary operative surgery and delayed closure. Others advocated early exploration and immediate closure; among the first to do so was the Austro-Hungarian otologist Robert Bárány. In 1918, the pioneer American neurosurgeon Harvey Cushing published well-documented proof of the desirability of definitive operative management done as soon as possible. Few World War I surgeons developed their knowledge of plastic surgery, neurosurgery and oral surgery in post-war practice. An exception was Henry Newland, who went on to pioneer the development of these specialties in Australasia. After World War II, the French plastic surgeon Paul Tessier created the multidisciplinary subspecialty of craniomaxillofacial surgery, with the help of his neurosurgical colleague Gérard Guiot, and applied this approach to the correction of facial deformities. It has become evident that the new subspecialty requires appropriate training programs.     

Clinical outcomes of facial transplantation: a review

A total of 18 composite tissue allotransplants of the face have currently been reported. Prior to the start of the face transplant programme, there had been intense debate over the risks and benefits of performing this experimental surgery. This review examines the surgical, functional and aesthetic, immunological and psychological outcomes of facial transplantation thus far, based on the predicted risks outlined in early publications from teams around the world. The initial experience has demonstrated that facial transplantation is surgically feasible. Functional and aesthetic outcomes have been very encouraging with good motor and sensory recovery and improvements to important facial functions observed. Episodes of acute rejection have been common, as predicted, but easily controlled with increases in systemic immunosuppression. Psychological improvements have been remarkable and have resulted in the reintegration of patients into the outside world, social networks and even the workplace. Complications of immunosuppression and patient mortality have been observed in the initial series. These have highlighted rigorous patient selection as the key predictor of success. The overall early outcomes of the face transplant programme have been generally more positive than many predicted. This initial success is testament to the robust approach of teams. Dissemination of outcomes and ongoing refinement of the process may allow facial transplantation to eventually become a first-line reconstructive option for those with extensive facial disfigurements.     

Guy Alexandre – An appreciation of his innovative contributions to organ transplantation

Guy Alexandre made major contributions to organ transplantation that, in my opinion, have not been sufficiently recognized by the transplant community. To make his contributions better known, I present a brief summary of the innovations for which he was largely responsible. As a research fellow at the Peter Bent Brigham Hospital in Boston in 1962–3, under subsequent Nobelist Joseph Murray, he contributed to the establishment of pharmacologic immunosuppressive therapy (initiated by Roy Calne) in patients undergoing renal allotransplantation. After his return to his native Belgium, he carried out the first clinical kidney transplant there and, controversially, was the first to take kidneys from brain-dead donors (in 1963), a major advance in organ transplantation. He was also the first to carry out an elective series of kidney transplants between ABO blood group-incompatible donors and recipients, using pre-transplant plasmapheresis to deplete anti-A/B antibodies. This led him to explore kidney xenotransplantation, reporting prolongation of function of pig kidneys in baboons in 1989. Finally, in the early 1990s, he investigated the concept of thymic tissue transplantation as a means of inducing tolerance to donor-specific allografts. I hope this summary of his work makes his pioneering contributions better known to the transplant community.     

应用整形外科原则治疗老年人面部皮肤肿瘤

目的探讨老年人面部肿瘤的手术治疗和整形修复问题。方法综合分析我院从2004年8月至2008年8月收治的47例老年面部皮肤肿瘤的临床资料,根据患者具体情况,制定个体化的治疗方案,方法包括直接切除、皮瓣转移和植皮修复。结果本组患者术后切口愈合良好,术区外形恢复满意,功能良好。结论应用整形外科原则治疗老年人面部浅表肿瘤,可恢复良好的外观和功能,值得临床推广。     

Transplantation activities in Iran

Iran is a tropical country with a land area of 1,648,000 square kilometers and a population of 68,100,000. Iran has a recorded history that dates back 2553 years. Its earliest medical school was Pasargad. Jondi Chapour University was founded 1753 years ago during the Sassanid dynasty as a center for higher education in medicine, philosophy, and pharmacology. Indeed, the idea of xenotransplantation dates back to days of Achaemenidae (Achaemenian dynasty), as evidenced by engravings of many mythologic chimeras still present in Persepolis. Avicenna (980-1037 AD), the great Iranian physician, performed the first nerve repair. Transplantation progress in Iran follows roughly the same pattern as that of the rest of the world, with some 10-20 years' delay. Modern organ transplantation dates back to 1935, when the first cornea transplant was performed at Farabi Hospital in Tehran, Iran. The first living-related kidney transplantation performed at Shiraz University Hospital dates back to 1968. The first bone marrow transplant was performed at Dr. Shariaati's Hospital in Tehran. The first heart transplant was performed 1993 in Tabriz, Iran. The first liver transplant was performed in 1993 in Shiraz. The first lung transplant was performed in 2001, and the first heart and lung transplants were performed in 2002, both at Tehran. In late 1985, the renal transplantation program was officially started in a major university hospital in Tehran and was poised to carry out 2 to 4 transplantations each week. Soon, another large center initiated a similar program. Both of these centers accepted surgical, medical, and nursing teams from other academic medical centers for training in kidney transplantation. Since 2002, Iran has grown to include 23 active renal, 68 cornea, 2 liver, 4 heart, 2 lung, and 2 bone marrow transplantation centers in different cities. In June 2000, the Organ Transplantation Brain Death Act was approved by the Parliament, followed by the establishment of the Iranian Network for Transplantation Organ Procurement. This act helped to expand heart, lung, and liver transplantation programs. By 2003, Iran had performed 131 liver, 77 heart, 7 lung, 211 bone marrow, 20,581 cornea, and 16,859 liver tranplantations. Sources of these donations were living-unrelated donor, 82%; cadaver, 10%; and living-related donor, 8%. The 3-year renal transplant patient survival rate was 92.9%, and the 40-month graft survival rate was 85.9%. Another large step in expanding the transplantation program is the construction of the Avi- Cenna (Abou Ali Sina) Transplant Hospital in Shiraz. This hospital hopefully will begin operation in 2 years. It will offer the opportunity for the exchange and sharing of organs and increased cooperation between transplant teams in the Middle East. The hospital offers great promise for transplant medicine in Iran and other Persian Gulf countries.     

Osteocutaneous face transplantation.

BACKGROUND: Facial transplantation has the potential to become a viable option in the treatment of acquired and congenital facial deformities. Transplantation of the bony maxillofacial skeleton with the soft tissues (osteocutaneous face transplantation) has not been performed clinically nor has it been described experimentally in a human cadaver model. METHODS: A mock osteocutaneous face transplant procedure was carried out on a cadaver model. The face was harvested in the subperiosteal plane and included the Le Fort III osseous segment. The allograft was inset by rigid internal fixation and soft tissue approximation. RESULTS: The face transplant procedure was technically feasible. On the basis of this experiment, review of prior investigations, and our experience in craniofacial surgery, the authors have identified 10 topics that present technical challenges specific to osteocutaneous transplantation of the face: customisation of the bony segment, sensory and motor innervation, extra-ocular movements, dentition, mastication, speech and swallowing, airway, vascular considerations, immunologic considerations, and identity issues. CONCLUSIONS: Once further advances in immunomodulatory therapy are made, face transplantation will likely still be reserved for only the most severe facial defects. Defects of such severity will likely include a substantial bony component in need of reconstruction. In addition to the challenges associated with facial allo-transplantation in general, there are many technical challenges associated specifically with osteocutaneous face transplantation. It is necessary to consider and discuss these challenges in anticipation of future advances that may allow composite face transplantation to become safe and clinically efficacious. This modality of transplantation has the potential to provide substantial benefit compared with autologous reconstruction.     

自体脂肪移植联合A型肉毒毒素在面部吸脂后凹陷患者中的应用效果

目的 探究自体脂肪移植与A型肉毒毒素治疗面部吸脂后凹陷的效果。方法 选取2020年4月-2022年 4月本院整形科收治的64例面部吸脂后凹陷患者为研究对象,随机分为对照组和观察组,各32例。对照组 给予自体脂肪移植治疗,观察组给予自体脂肪移植联合A型肉毒毒素治疗,比较两组临床疗效、并发症发 生情况及脂肪组织坏死情况。结果 观察组治疗总有效率为96.88%,高于对照组的81.25%（P＜0.05）;观察 组并发症总发生率为0,低于对照组的18.75%（P＜0.05）;观察组自体脂肪组织坏死率为3.13%,低于对照 组的18.75%,但差异无统计学意义（P＞0.05）。结论 自体脂肪移植联合A型肉毒毒素在面部吸脂后凹陷患 者中的应用效果确切,可有效改善患者面部凹陷问题,提高其面部流畅度及美观度,同时能够促进移植脂 肪成活,降低不良反应发生几率,应用安全性较高。     

Donor operation for face transplantation

The first clinical face allotransplantation was performed by Devauchelle et al in 2005, and currently 13 facial allotransplantations have been performed worldwide. Reports on almost half of the cases were published in the literature, focusing on technical details of facial allograft inset to the recipient face. There are only few reports describing technical details of recovery of the facial allograft from the human donor. In this article, we summarize our cadaveric studies describing the methods of facial flap recovery in the cadaveric model and as well as mock facial transplantation. Based on our experience with the first case of face transplantation, we describe the sequence of facial graft procurement from the human donor and compare similarities and differences between our case and previously published cases. Furthermore, we discuss different methods of restoration of the donor face and have outlined proposed guidelines for the sequence of donor operation for facial graft procurement.     

Heart transplantation in the early phase of the COVID-19 pandemic: A single-center case series

The infectious disease coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. The impact of COVID-19 on solid organ transplantations, including heart transplantation, is currently unclear. Many transplant programs have been forced to swiftly re-evaluate and adapt their practices, leading to a marked decrease in transplants performed. This trend has been due to various factors, including increased donor COVID-19 screening scrutiny and recipient waiting list management in anticipation of COVID-19 critical care surge capacity planning. In the face of these unknown variables, determining when and how to proceed with transplantation in our population of patients with end-stage cardiomyopathies is challenging. Here, we describe our center's experience with orthotopic heart transplantation (OHT) in one of the country's pandemic epicenters, where we performed eight OHTs in the first 2 months after community spread began in late February 2020.     

Overview of Guidelines for Establishing a Face Transplant Program: A Work in Progress

Since 2005, nine face transplants have been performed in four countries: France, the United States (US), China and Spain. These encouraging short‐term outcomes, with the longest survivor approaching 5 years, have led to an increased interest in establishing face transplant programs worldwide. Therefore, the purpose of this article is to facilitate the dissemination of relevant details as per our experience in an effort to assist those medical centers interested in establishing a face transplant program. In this article, we address the logistical challenges involved with face transplantation; including essential program requirements, protocol details, face transplant team assembly, project funding, the organ procurement organization and the coroner. It must be emphasized that face transplantation is still experimental and its therapeutic value remains to be validated. All surgical teams pursuing this endeavor must dedicate an attention to detail and should accept a responsibility to publish their outcomes in a transparent manner in order to contribute to the international field. However, due to its inherent complexity, facial transplantation should only be performed by university‐affiliated medical institutions capable of orchestrating a specialized multidisciplinary team with a long‐term commitment to its success.     

Heterotopic cardiac transplantation. A 7-year experience at Groote Schuur Hospital, Cape Town

Between November 1974 and February 1982 40 patients underwent heterotopic heart transplantation at Groote Schuur Hospital, Cape Town. In 4 of these patients retransplantation was carried out, bringing the total number of heterotopic heart transplant operations to 44. Fourteen patients are alive to date, from 4 months to more than 7 years after transplantation. The 1-year survival rate has been 60%. Three of the first 6 patients in this series have survived for 6 years or more, while 6 of the 7 patients who received transplants during 1981 (including 2 who underwent retransplantation) are alive. Retransplantation of the donor heart, donor heart procurement from distant sources using prolonged myocardial preservation techniques and the reasons why heterotopic cardiac transplantation is more advantageous than other methods are discussed. The surgical technique and some modifications introduced since this method was first described in 1975 are presented in detail.     

Treatment of chronic renal failure by transplantation and dialysis: two decades of cooperation.

The overall transplant experience at the Peter Bent Brigham Hospital which extends over twenty years has been reviewed; the course of all patients was updated to a followup of at least one year (through October 1973). A total of 388 patients received 427 renal isografts and allografts between March 1951 and October 1972. Of these, 58% were still alive at the end of the followup period, 50% with a functioning graft. The results of patient and allograft survival early (1959-1968) and later (1968-1973) in the experience have been compared. The significant decline in patient mortality, especially among recipients of cadaver allografts, demonstrates improved treatment of complications and increased availability of dialysis. The improvement of allograft function during the two time periods is less striking but still significant. Overall social and work rehabilitation following transplantation was evaluated in 284 patients, 86% of whom became at least as well adjusted as they had been prior to the development of renal failure. The incidence and individual causes for mortality and complications of transplantation have been compared to results from the National Dialysis Registry, figures comparable to those of the dialysis program at this institution. Transplantation and dialysis must be used conjointly and in a complimentary manner as part of the total treatment for those with end-stage renal failure.     

Correction of hemifacial atrophy with autologous fat transplantation

BACKGROUND: Autologous fat transplantation has frequently been used by many surgeons for facial recontouring in esthetic patients, with good long-term results. However, this technique has not been used primarily in treating patients with hemifacial atrophy, and its efficacy and long-term outcome remain unknown. METHODS: In a 7-year period, 31 patients with hemifacial atrophy were treated with autologous fat transplantation in our institution. All patients had been in their stable phase of the disease for at least 1 year. Autologous fat grafts were harvested from the lower abdomen or thigh with our preferred low-pressure syringe technique and then spun at the lower speed. The fat grafts were injected into multiple areas in multiple tissue planes and tunnels to the diseased side of the face. The same procedure was repeated once or twice as necessary after each injection in at least 3 months. All patients were followed up to 5 years, and their outcomes were evaluated by the patients, plastic surgeons, and laypersons separately. RESULTS: Obviously improved facial contour was evident in most patients after autologous fat transplantations. More than 65% of the patients in this series were assessed as satisfactory by all 3 groups. Between 10% and 30% of the patients were mostly satisfactory. Only less than 7% of the patients were unsatisfactory. No complications were seen in either donor sites or recipient sites in this series. CONCLUSIONS: Autologous fat transplantation can be a good treatment of choice for patients with hemifacial atrophy.